Exposure to stressful events is a key factor in the etiology of several mood and anxiety disorders. However, not all individuals exposed to stressful events develop stress-related mental illness, and there is considerable interest in what makes some individuals vulnerable and others resilient. In this proposal, we will investigate the neural substrates and cellular mechanisms controlling resistance to social stress using a social defeat model in Syrian hamsters, called conditioned defeat. Our previous research indicates that neural activity in the infralimbic (IL) and prelimbic (PL) cortex is necessary for the reduced conditioned defeat response exhibited by dominant hamsters. In general, we expect that the maintenance of dominance relationships generates plasticity in specific neural circuits that promotes resistance to conditioned defeat in dominant hamsters. In this proposal, we hypothesize that activation of IL neurons with efferent projections to the basolateral amygdala (BLA) (i.e. IL-to-BLA neural circuit) and PL neurons with efferent projections to the dorsal raphe nucleus (DRN) (i.e. PL-to-DRN neural circuit) regulates resistance to conditioned defeat in dominant hamsters. We will test two specific aims in this proposal. First, we will determine whether elevated defeat- induced neural activation in dominant hamsters occurs within IL-to-BLA and/or PL-to-DRN neural circuits. Second, we will determine whether selective inhibition of IL-to-BLA and/or PL-to-DRN neural circuits prevents resistance to conditioned defeat in dominant hamsters. This line of research will improve our understanding of the neural mechanisms controlling resistance to social stress and will identify novel targets for the prevention and treatment of stress-related mental illness.